The increasing use of second-generation antipsychotics (SGAs) among children over the last two decades despite emerging evidence regarding the metabolic side effects of these agents has triggered increasing public concern.3-8 The majority of SGA use today is non-FDA-approved or 'off-label'use to treat aggressive or behavioral symptoms. SGAs are most frequently given to children with Attention Deficit Hyperactivity Disorder (ADHD) and to children in foster care, who among all Medicaid-enrolled children, have the highest rates of mental health service use and are most likely to have disruptive behaviors.7, 9 Despite these concerns, there are currently no national standards for monitoring SGA safety in pediatric populations. Additionally, the literature lacks evidence documenting the magnitude and prevalence of SGA use and the risk of adverse events in a national sample of children. The broad goal of the proposed research is to generate an evidence- base for SGA use in pediatric populations with a long-term goal to develop programs and policies that promote more effective and safe medication practices, and ultimately improve outcomes. These analyses will use national Medicaid data to identify a cohort of children with ADHD who are Medicaid eligible on the basis of poverty, foster care, or disability with the aims to: 1) Examine the variation across states and over time in the exposure to SGAs from 2001-2006 among a national cohort of children with ADHD, stratified by Medicaid eligibility subgroups (e.g. poverty, foster care, and disability);2) Identify whether system- level factors (e.g. physician resources, health system organization, child welfare organization and policies) modify the risk of exposure to SGAs among children;3) Create multivariate matched cohorts of treated and untreated children as a means to quantify risk of hypertension and diabetes among children exposed to SGAs;4) Identify clinical factors (e.g. choice of antipsychotic, daily dose, prior exposure to psychotropic medication) that may modify the risk for adverse events among children receiving SGAs. The major contribution of this proposal is the use of a national database to evaluate the risk factors for adverse events associated with SGAs in pediatric populations so that we may establish standards for safe medication practices that can be implemented into system-level programs and policies. The adverse events can only be studied feasibly with national data as proposed for this study. The research also directly addresses the convergence of NIMH, federal and state policy priorities.11-13 Findings will be framed to help states and local municipalities identify opportunities for practice and systems-change in their communities. PUBLIC HEALTH RELEVANCE: The increasing use of second-generation antipsychotics (SGAs) among children over the last two decades despite emerging evidence regarding the metabolic side effects of these agents is indicative of a significant gap between effective program policies and safe medical practice. Using national Medicaid data, this project will examine the growth and variation in SGA use across the country and over time in a group of high-risk children with ADHD, identify system level factors influencing the use of SGAs, quantify the risk for serious metabolic side effects of SGA use in children, and identify clinical factors that may modify the risk of adverse events among children receiving SGAs.